title: Genetic characterization and protein stability analysis of a Chinese family with Von Hippel-Lindau disease.
abstract: BACKGROUND
  Von Hippel-Lindau disease (VHL), a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems, has rarely been reported in Asia. We genetically investigated a unique Chinese family with VHL disease and performed an analysis of the VHL protein stability.
  
  
  METHODS
  Genomic deoxyribonucleic acid (DNA) extracted from peripheral blood was amplified by polymerase chain reaction (PCR) to three exons of the VHL gene in 9 members of the Chinese family with VHL disease. PCR products were directly sequenced. We estimated the effects of VHL gene mutation on the stability of pVHL, which is indicated by the free energy difference between the wild-type and the mutant protein (ΔΔG).
  
  
  RESULTS
  The Chinese family was classified as VHL type 1. Three family members, including two patients and a carrier, had a T to G heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1. This missense mutation resulted in the transition from leucine to arginine in amino acid 101 of the VHL protein. There was low stability of the VHL protein (the ΔΔG was 12.71 kcal/mol) caused by this missense mutation.
  
  
  CONCLUSIONS
  We first reported a family with this VHL gene mutation in Asia. This missense mutation is predicted to significantly reduce the stability of the VHL protein and contribute to the development of the renal cell carcinoma (RCC) phenotype displayed by this family. The genetic characterization and protein stability analysis of families with VHL disease are important for early diagnosis and prevention of the disease being passed on to their offspring.
authors.affiliation: Reproductive Medicine Center, The Key Laboratory for Reproductive Medicine of Guangdong Province, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.forename: Yan-ping
authors.initials: YP
authors.lastname: Huang
authors.forename: Xiang-an
authors.initials: XA
authors.lastname: Tu
authors.forename: Dao-sheng
authors.initials: DS
authors.lastname: Luo
authors.forename: Dao-hu
authors.initials: DH
authors.lastname: Wang
authors.forename: Shao-peng
authors.initials: SP
authors.lastname: Qiu
authors.forename: Peng
authors.initials: P
authors.lastname: Xiang
authors.forename: Wei-qiang
authors.initials: WQ
authors.lastname: Li
authors.forename: Rohozinski
authors.initials: R
authors.lastname: Jan
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Xiang-zhou
authors.initials: XZ
authors.lastname: Sun
authors.forename: Chun-hua
authors.initials: CH
authors.lastname: Deng
mesh_terms: D000328:Adult; D002681:China; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D055550:Protein Stability; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000737:chemistry / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human